The long-term objective of this research is to further our understanding of the structure and function of IgA-type antibodies and certain other components present in nonvascular fluids which may participate in the resistance of mucous surfaces to invasion by potential damaging agents. It is proposed to study the structure and site of binding of secretory component and to determine the structure of an enzyme, IgA protease, which splits both serum and secretory IgA. The complement fixing properties of the Fc alpha fragment produced by several new techniques will be investigated. A major emphasis will be placed on the cells of the GI tract involved in regulation of the local and possibly system immune responses; specifically, the role of suppressor cells in oral tolerance to sheep red blood cells and dinitrochlorobenzene (DNCB). In the DNCB system, it is proposed to isolate and characterize chemically by sequence studies the structure of a suppressive factor of T cell origin, possibly involved in tolerance. Patients with a selective deficiency of IgA who also mainfest a mucosal deficiency will be studied to determine whether different groups exist, some lacking helper cells or factors and others with excessive suppressive influences. We will also attempt to initiate IgA secretion by these patients' cells in vitro by procedures which alter and/or help suppression using methods that could have potential therapeutic applications. The secretion-specific lactoferrin and its serum analogue transferrin will be studied for a new enzymatic role in thiol oxidations postulated on the basis of our preliminary work, and the apparent requirement for these proteins in certain immune reactions explored in more detail.